Overview
This lecture compares the two major pyogenic gram-positive cocci of skin and soft tissue infection, Staphylococcus aureus and Streptococcus Pyogenes: their shared and distinguishing features, their virulence factors, and the spectrum of skin/soft tissue disease they cause, which worsens with increasing depth of tissue involvement (pyodermas → cellulitis/erysipelas → necrotizing fasciitis). It closes with diagnosis and treatment principles and a brief note on other clinically important staphylococci and streptococci.
S. aureus vs S. pyogenes: shared and distinguishing features
What they have in common:
- Facultative anaerobic gram-positive cocci
- Beta-haemolysis on blood agar (BA)
- Part of the microbiome
- Opportunistic pathogens
- Cause similar infections and can co-infect
- Similar virulence factors, including superantigens, pro-inflammatory teichoic acids and peptidoglycan, toxins, adhesins, invasins (tissue-destroying enzymes) and immune evasion strategies (biofilms, capsules)
- There is a direct relationship between virulence traits and clinical disease: more virulence factors = more pathogenic = more chance of infection. Traits are variable between strains (e.g. not all S. aureus strains have epidermolytic toxin; not all S. pyogenes strains have erythrogenic toxin)
Distinguishing features:
| Feature | S. aureus | S. pyogenes |
|---|---|---|
| Gram stain morphology | Clusters | Chains |
| Catalase | Positive | Negative |
| Coagulase | Positive | Negative (not produced) |
| Penicillin susceptibility | >50% resistant | Susceptible |
| Typical infection pattern | Localized (abscesses) | Spreading |
| Antimicrobial resistance | More resistant | Less resistant |
| Colony colour on BA | Golden (carotenoid pigment, an antioxidant virulence factor protecting from ROS) | - |
Carriage/microbiome:
- S. aureus: ~30% nasal carriage (50-90% in healthcare workers, HCW); also found on skin (apocrine areas: perineum, groin, axillae), oral cavity, upper respiratory tract (URT), GIT, genitourinary tract (GUT)
- S. pyogenes: 5-15% pharyngeal carriage; disease is associated with acquisition of a new strain or a change in host status
Catalase test: H2O2 -> H2O + O2; catalase-positive organisms (S. aureus) are more resistant to intracellular killing.
Virulence factors
Both organisms possess toxins, enzymes (invasins), immune evasion molecules and surface adhesion molecules (selected factors only; not all present in every strain).
S. aureus
- Toxins: Panton-Valentine leukocidin (PVL), alpha-toxin, phenol-soluble modulins, epidermolytic toxin, superantigens
- Enzymes (invasins): collagenase, hyaluronidase, DNase, lipase, coagulase, staphylokinase, haemolysins
- Immune evasion: protein A, capsule (fibrin), biofilms
- Adhesion molecules: MSCRAMMs, SERAMs, teichoic acids
S. pyogenes
- Enzymes (invasins): C5a peptidase, streptokinase, streptolysins (haemolysins), hyaluronidase, DNase
- Toxins: erythrogenic/pyrogenic toxins (superantigens)
- Immune evasion: M protein, capsule (hyaluronic acid), protein G, biofilms
- Surface adhesion molecules: teichoic acids, F protein, M protein
Selected virulence mechanisms in detail
PVL (S. aureus): a leukocidin that kills neutrophils; a pore-forming cytotoxin that inserts into the cell membrane causing lysis, releasing cell contents and causing further cell/tissue damage. Associated with necrotising pneumonia, necrotising fasciitis and sepsis. MRSA strains are typically PVL-positive.
Coagulase (S. aureus): exists in two forms.
- Free coagulase: secreted, converts prothrombin to thrombin; contributes to abscess formation
- Bound coagulase: on the cell wall, converts fibrinogen to fibrin; contributes to immune evasion/clumping
Both act on the terminal common pathway of the coagulation cascade (prothrombin -> thrombin; fibrinogen -> fibrin -> cross-linked clot).
M protein (S. pyogenes):
- Antigenic variation (>150 types), giving limited cross-protective immunity
- Negatively charged, so repels phagocytes
- Inhibits C3b, preventing opsonisation
- Binds fibronectin, acting as an adhesin
- Linked to rheumatic fever: cross-reactive antibody-mediated inflammation against heart tissue (myosin); subsequent infections worsen heart damage, leading to rheumatic heart disease
- Linked to glomerulonephritis: immune complex/complement-mediated
- Treating pharyngitis in risk groups stops both the development of rheumatic fever and transmission of rheumatic-fever-causing strains
M protein is a single molecule responsible for immune evasion, adhesion, and (via cross-reactive antibodies) the post-infectious complications of rheumatic fever and glomerulonephritis.
Skin and soft tissue infection spectrum
Severity and risk of complication increase with increasing depth of tissue involvement: pyodermas (superficial) -> cellulitis/erysipelas (mid-level) -> necrotizing fasciitis (deep, fascial). Deeper infections (cellulitis and necrotizing fasciitis) can also be gram-negative or polymicrobial (mixed gram-positive/gram-negative, aerobic/anaerobic), unlike the superficial pyodermas.
By depth (cutaneous anatomy correlate): epidermis (impetigo), superficial (folliculitis, furunculosis, carbunculosis, ecthyma), mid-level (cellulitis), fascia (necrotizing fasciitis), muscle (myonecrosis, clostridial and non-clostridial).
Impetigo
- Non-bullous: caused by S. aureus and/or S. pyogenes; mostly children, usually around the mouth; thin-walled vesicle on an erythematous base that lyses and dries to form “honey”-coloured crusts
- Bullous: caused by S. aureus producing epidermolytic exotoxin; forms fluid-filled vesicles (bullae); affects all ages; may occur anywhere on the body
- Diagnosis: clinical presentation; culture of bullous/serous fluid can guide antimicrobial choice
Folliculitis: infection of hair follicles; small papules evolve into pustules; superficial. Caused by S. aureus (coagulase, adhesins); pus may be cultured. Self-limiting; treated with topical antiseptics/wound care, or oral antimicrobials if disease is extensive, topical treatment fails, or infection progresses.
Furuncle (boil): arises from folliculitis as a deeper infection of the hair follicle with pus and local cellulitis. Caused by S. aureus (coagulase, adhesins); pus can be cultured. Complications: abscesses, cellulitis. Risk factors: diabetes, obesity, S. aureus carriage, immunosuppression. Treatment: surgical drainage plus oral/IV antimicrobials.
Carbuncle: extensive infection of follicles, usually neck, back or thighs; caused by S. aureus (PVL-positive, coagulase-positive); causes systemic symptoms (fever, nausea). Risk factors: age (elderly), diabetes, prolonged steroid therapy. Clinical course: painful, hard lump; suppuration begins after 5-7 days with pus discharge from follicles; may progress to necrosis and ulceration. Diagnosis: culture of pus with antimicrobial sensitivities. Treatment: surgical drainage plus oral/IV antimicrobials.
Cellulitis: a spreading process involving the dermis and hypodermis; can be small (redness around acne) or large (an entire limb).
- Symptoms: little/no necrosis with oedema; ill-defined margins that merge smoothly with adjacent skin; reddish fading to pink; pain, heat, swelling, erythema; fever, chills, nausea, leukocytosis; bacteraemia occurs in 30% of cases
- Complications: abscess, osteomyelitis, septic arthritis, sepsis, necrotizing fasciitis
- Most common causative agents: S. aureus, S. pyogenes (via wounds/post-surgery, using invasins and toxins); also other gram-positive cocci (enterococci, staphs, streps), gram-negative rods, and anaerobes; may be polymicrobial
- Risk factors: trauma, diabetes, vascular disease, pregnancy, obesity, immune deficiency, age
- Diagnosis: clinical; culture of aspirates, abscesses, pustules, wounds; blood cultures if febrile; antimicrobial sensitivities
- Treatment: depends on extent of infection, host status and causative organism; empiric therapy given the risk of complication
Erysipelas: a form of superficial cellulitis with lymphatic involvement, caused by S. pyogenes using invasins.
- Symptoms: bright red, well-demarcated, indurated, oedematous lesion; systemic symptoms (fever, chills, malaise, leukocytosis); typically affects legs/face; mostly elderly, children and infants
- Risk factors: immune deficiency, diabetes, alcoholism, age, skin ulceration, impaired lymphatic drainage
- Complications: sepsis, septic arthritis, infective endocarditis, lymphatic damage, necrotising fasciitis
- Treatment: oral or IV, dependent on severity/host status
Necrotizing fasciitis: a rapid, spreading, destructive infection along the fascia (the fibrous connective tissue between skin and muscle).
- Mortality: >90% if treatment is delayed; ~20% even after aggressive therapy; can progress to sepsis and multi-organ failure. An initial wound is often trivial-looking but can progress to extensive necrosis within hours.
- Caused by S. pyogenes or S. aureus, using tissue-destroying enzymes (invasins), superantigens and toxins; most infections, however, are polymicrobial (aerobic/anaerobic, gram-positive and gram-negative)
- Risk factors: diabetes, obesity, vascular disease, injecting drug use (IDU), immunosuppression, smoking, elderly, male
- Diagnosis, clinical: oedematous, erythematous, intensely painful, warm and tender tissue; rapidly advancing cellulitis; tissue discolouration progressing to necrosis, inflammation, blistering; fever, malaise, diarrhoea, headache, vomiting, dehydration
- Diagnosis, laboratory: culture and antimicrobial sensitivities from biopsy of wound margins or deep tissues (Gram stain helpful to direct empiric therapy); blood cultures
Treatment principles
- Minor skin infections (pyodermas) may not require antimicrobials if wound care and topical antiseptics are effective; oral antimicrobials are used if the infection fails to respond, progresses, or the patient is at risk
- Abscesses (furuncles/carbuncles): surgical drainage, plus or minus oral/IV antimicrobials
- Cellulitis: oral/IV antimicrobials, with empiric therapy started initially given the risk of complication in at-risk patients
- Necrotising fasciitis: IV antimicrobials (initially empiric) plus surgical debridement (which may include amputation)
- S. aureus: >50% of strains are penicillin resistant, so flucloxacillin is used; MRSA (flucloxacillin-resistant) requires vancomycin
- S. pyogenes: remains susceptible to penicillin; macrolides are used in penicillin allergy
Other important staphylococci and streptococci
- S. epidermidis: causes healthcare-associated infections (HAI), particularly device-associated biofilm infections (bloodstream infection/BSI, UTI, infection of implants); >40% of isolates are resistant to flucloxacillin
- S. saprophyticus: causes UTI, particularly in young women
- S. agalactiae: causes neonatal infections (premature infants at risk), including pneumonia, meningitis, sepsis
- S. pneumoniae: causes pneumonia, meningitis, sepsis, otitis media
- Enterococcus: causes HAI, particularly device-associated biofilm infections (UTI, wound infections, endocarditis); notable for antimicrobial resistance
Epidemiology and summary points
- A gram-positive coccus seen in clinical samples is likely staphylococcus (clusters, catalase-positive) or streptococcus (pairs/chains, catalase-negative)
- As part of the microbiome: S. aureus is carried by ~30% of people (mainly nose, also skin, URT, GIT, UGT); S. pyogenes by ~15% (skin, URT)
- Skin infection is a common presentation; disease/severity depends on microbial virulence, site of infection and host response. S. aureus tends to cause localized infections (abscesses); S. pyogenes tends to cause spreading infections
- Rates of skin infection are high in New Zealand, with Maori, Pasifika and children most affected
- Treatment: S. aureus - penicillin resistance is common so flucloxacillin is first line, with vancomycin for MRSA (flucloxacillin-resistant); S. pyogenes - penicillin
Self-test
- Distinguish S. aureus from S. pyogenes by Gram stain morphology, catalase status, coagulase status, penicillin susceptibility and typical infection pattern.
- What features do S. aureus and S. pyogenes have in common?
- Describe the two forms of coagulase produced by S. aureus and what each does.
- Describe the mechanism by which PVL damages cells, and name three conditions it is associated with.
- List the four categories of virulence factor shown for S. aureus and give one example of each.
- Describe the roles of M protein in S. pyogenes virulence and immune evasion.
- Explain how M protein antibodies lead to rheumatic fever and rheumatic heart disease.
- Distinguish non-bullous from bullous impetigo in terms of causative organism, typical age group and clinical appearance.
- A patient presents with a painful, hard lump on the neck that has been discharging pus from multiple follicles for a week, with fever and nausea. What is the likely diagnosis, likely organism, and what risk factors would you ask about?
- List, in order of increasing severity/depth, the skin and soft tissue infections covered in this lecture.
- Describe the clinical features that distinguish cellulitis from erysipelas.
- What proportion of cellulitis cases are complicated by bacteraemia?
- Why is necrotizing fasciitis dangerous even when the initial wound looks trivial, and what are its mortality figures with and without delayed treatment?
- Outline the diagnostic approach (clinical and laboratory) to suspected necrotizing fasciitis.
- What antimicrobial is used to treat penicillin-resistant S. aureus, and what is used if the strain is also flucloxacillin-resistant (MRSA)? What is used to treat S. pyogenes, including in penicillin allergy?
- Name the causative organisms and typical patient groups for: device-associated biofilm HAI in a coagulase-negative staphylococcus, UTI in a young woman, and neonatal pneumonia/meningitis/sepsis.
Answers
Reveal answers
- S. aureus: clusters, catalase-positive, coagulase-positive, >50% penicillin resistant, tends to cause localized infections (abscesses). S. pyogenes: chains, catalase-negative, coagulase-negative, penicillin-susceptible, tends to cause spreading infections.
- Both are facultative anaerobic gram-positive cocci, show beta-haemolysis on blood agar, are part of the normal microbiome, are opportunistic pathogens, cause similar infections and can co-infect, and share broadly similar categories of virulence factor (toxins, enzymes/invasins, immune evasion, adhesion molecules), though the specific molecules differ.
- Free coagulase is secreted and converts prothrombin to thrombin, contributing to abscess formation. Bound coagulase is on the cell wall and converts fibrinogen to fibrin, contributing to immune evasion and clumping.
- PVL is a pore-forming cytotoxin (leukocidin) that inserts into the neutrophil cell membrane, causing lysis and release of cell contents, which causes further tissue damage. It is associated with necrotising pneumonia, necrotising fasciitis and sepsis (MRSA strains are typically PVL-positive).
- Toxins (e.g. PVL), enzymes/invasins (e.g. coagulase), immune system evasion (e.g. protein A), and adhesion molecules (e.g. MSCRAMMs).
- M protein shows antigenic variation (>150 types, limiting cross-protective immunity), is negatively charged so repels phagocytes, inhibits C3b to prevent opsonisation, and binds fibronectin to act as an adhesin.
- Antibodies produced against M protein cross-react with self-tissue (heart, myosin), causing antibody-mediated inflammation; subsequent infections worsen the heart damage, leading to rheumatic heart disease.
- Non-bullous impetigo is caused by S. aureus and/or S. pyogenes, mostly affects children around the mouth, and produces thin-walled vesicles on an erythematous base that dry into honey-coloured crusts. Bullous impetigo is caused by S. aureus producing epidermolytic exotoxin, affects all ages and any body site, and produces fluid-filled bullae.
- Carbuncle, likely S. aureus (PVL-positive, coagulase-positive). Risk factors to ask about: age (elderly), diabetes, prolonged steroid therapy.
- Pyodermas (impetigo, folliculitis, furuncle, carbuncle) -> cellulitis/erysipelas -> necrotizing fasciitis.
- Cellulitis has ill-defined margins that merge smoothly into surrounding skin, with reddish colour fading to pink, and involves the dermis and hypodermis (caused by S. aureus and/or S. pyogenes). Erysipelas is a superficial form of cellulitis with lymphatic involvement, caused by S. pyogenes, with a bright red, well-demarcated, indurated, oedematous lesion, typically on the legs or face.
- 30% of cellulitis cases have bacteraemia.
- The initial wound is often trivial-looking but the infection spreads rapidly along the fascia, destroying tissue and progressing to sepsis and multi-organ failure sometimes within hours. Mortality is >90% if treatment is delayed, and ~20% even after aggressive therapy.
- Clinically: oedematous, erythematous, intensely painful, warm and tender tissue with rapidly advancing cellulitis, tissue discolouration/necrosis/blistering, and systemic features (fever, malaise, diarrhoea, headache, vomiting, dehydration). Laboratory: culture and antimicrobial sensitivities from biopsy of wound margins/deep tissue (Gram stain helps direct empiric therapy), and blood cultures.
- Penicillin-resistant S. aureus is treated with flucloxacillin; MRSA (flucloxacillin-resistant) is treated with vancomycin. S. pyogenes is treated with penicillin, or macrolides if the patient is penicillin-allergic.
- S. epidermidis causes device-associated biofilm HAI (BSI, UTI, implant infection). S. saprophyticus causes UTI in young women. S. agalactiae causes neonatal pneumonia, meningitis and sepsis (premature infants at risk).